Abstract

Prostate cancer (PCa) represents a major health burden to the US male population. In particular, African Americans are disproportionately affected by this disease as they are twice more likely to be diagnosed and die from PCa than European American men . In order to identify genetic factors that may predispose individuals to PCa we employed an admixture mapping strategy that takes advantage of the mixed ancestry of the African American population. African American cases and controls (N=557) from the Washington DC area were genotyped at 105 ancestry informative markers (AIMs) along chromosome 12 and at an additional 103 AIMs distributed across the genome. The programs STRUCTURE, STRAT and ADMIXMAP were used to estimate individual and locus-specific ancestry and to test for association between the AIMs and PCa while accounting for population stratification that may arise as a result of admixture. Sixteen markers located between chromosomal positions 22Mb and 115Mb showed an association with PCa at a significance level of 0.05, after correction for individual ancestry. Five of the associated AIMs were found within a gene, that included VDR and CYP27B1. Four additional SNPs were typed in each of these genes, which are well-know candidates for PCa given their involvement in the vitamin D pathway. No association with disease status was found for any of the extra SNPs. Our results indicate that chromosome 12 is likely to harbour one or more PCa susceptibility loci but further fine mapping studies are warranted to narrow these regions down and isolate the causal variants.